Grant-funded Project Nr. 021/1999/B-CH/FaF
Final Report

Project title:Preparation of benzylthio derivatives of nitrogen heterocycles with antimycobacterial and antifungal activity
Research leader:Doc.RNDr. Věra Klimešová, CSc.
Co-researcher: Mgr. Jiří Gregor; Ing. Jan Kočí; Ing. Ota Bureš; Ing. Pavel Holý; Ing. Milan Peřina; Mgr. Lenka Zahájská
Period of project:1999-2001
Overall grant:355 000 CZK

Project Results

Series of 2-benzylsulfanyl derivatives of benzimidazole, 5-methylbenzimidazole, benzothiazole, benzoxazole and 3-benzylsulfanyl derivatives of 1,2,4-triazole and 5-methyl-1,2,4-triazole were prepared and the compounds were evaluated in vitro for antimicrobial activity. The compounds were modified in benzyl moiety by groups with electron-accepting and electron-donated properties. The structures of the compounds were confirmed by IR and NMR data, and their purity by elemental analysis. Mycobacterium tuberculosis and non-tuberculous mycobacteria were use for the antimycobacterial evaluations.  The compounds exhibited activity against all mycobacterial strains. The MIC values are within a range 4-1000  m mol/l, the most active set of 5-methylbenzimidazole displaed the MIC values 4-62 m mol/l  and exceeded the efficacy of the standard isoniazide against non-tuberculous strains. The nitro and thioamide derivatives were the most active compounds in all sets. According to the QSAR study, the activity increases with electron-accepting groups in benzyl moiety, the hydrophobicity is important for activity against M. avium. The antifungal activity of prepared compounds was evaluated against the potentially pathogenic fungi (yeasts, dermathophytes and filamenous fungi). The sets of benzimidazole and triazole were tested. The compounds revealed a weak activity. The MIC values are within a range 62-1000 m mol/l. Triazole derivatives with halogene on the benzyl moiety were the most active compounds.  Trichophyton mentagrophytes was the most sensitive strains. The most antimycobacterial active compounds were subjected to an antiproliferative (K-562 and L-929 cell) and cytotoxic (HeLa cell) effect. According to the values of GI and CC, compounds can be considered as moderately toxic.